Oral squamous cell carcinoma is a condition that will kill approximately half of patients afflicted within five years of diagnosis and may leave surviving patients with severe aesthetic and/or functional compromise. Oral cancer progresses through a series of morphologic changes, which if treated early, vastly improve prognosis. The biochemical and molecular changes preceding the morphologic progression of oral lesions are poorly understood. Development of a novel integrated optical technique for non- invasive characterization and monitoring of the biochemical and morphological changes that occur during tissue transformation in oral cavity epithelium leading to dysplasia and ultimately to invasive squamous cell carcinoma is proposed. A currently available optical coherence tomography (OCT) imaging endoscope will be combined with a fluorescence imaging system using a novel probe designed to allow integration of the two imaging modalities. The proposed novel integrated system will allow for fluorescence image- guided screening of oral tissue as well as accurate OCT imaging at the same location. Fluorescence imaging will provide a highly sensitive and rapid means for non-invasive identification of suspicious lesions, while OCT imaging will allow detailed morphologic characterization in such lesions. The proposed integrated OCT/fluorescence imaging probe is expected to demonstrate a high degree of sensitivity and specificity for early non-invasive detection of both superficial pre-malignant and malignant lesions in the oral cavity. Experiments are proposed that will allow for assessing the correlation between histopathogical assessment of tissue during malignant transformation and the spectroscopic and morphologic changes in tissue structure as detected by fluorescence and OCT images respectively. In the phase l of this project, the proposed innovative system will be designed, developed and tested in a series of preclinical animal studies in a well established model for oral cancer. PROPOSED COMMERCIAL APPLICATIONS: A diagnostic device that can rapidly and non-invasively detect superficial lesions with a high degree of sensitivity and specificity can be used for early detection of various superficial pre-malignant and malignant lesions. Such a system will be used by various medical specialties including dentists, ENT, endoscopists and gynecologists. In addition, the proposed device may be used intraoperatively by surgeons in order to perform rapid tissue identification and ensure that the malignant tissue remaining in the tumor bed is removed surgically. Thus successful development of the proposed system will offer a considerable potential for commercial success.